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Drug Overdose and Suicide Among Veteran Enrollees in the VHA: Comparison Among Local, Regional, and National Data
Suicide is the 10th leading cause of death in the US. In 2017, there were 47,173 deaths by suicide (14 deaths per 100,000 people), representing a 33% increase from 1999.1 In 2017 veterans accounted for 13.5% of all suicide deaths among US adults, although veterans comprised only 7.9% of the adult population; the age- and sex-adjusted suicide rate was 1.5 times higher for veterans than that of nonveteran adults.2,3
Among veteran users of Veterans Health Administration (VHA) services, mental health and substance use disorders, chronic medical conditions, and chronic pain are associated with an increased risk for suicide.3 About one-half of VHA veterans have been diagnosed with chronic pain.4 A chronic pain diagnosis (eg, back pain, migraine, and psychogenic pain) increased the risk of death by suicide even after adjusting for comorbid psychiatric diagnoses, according to a study on pain and suicide among US veterans.5
One-quarter of veterans received an opioid prescription during VHA outpatient care in 2012.4 Increased prescribing of opioid medications has been associated with opioid overdose and suicides.6-10 Opioids are the most common drugs found in suicide by overdose.11 The rate of opioid-related suicide deaths is 13 times higher among individuals with opioid use disorder (OUD) than it is for those without OUD.12 The rate of OUD diagnosis among VHA users was 7 times higher than that for non-VHA users.13
In the US the age-adjusted rate of drug overdose deaths increased from 6 per 100,000 persons in 1999 to 22 per 100,000 in 2017.14 Drug overdoses accounted for 52,404 US deaths in 2015; 33,091 (63.1%) were from opioids.15 In 2017, there were 70,237 drug overdose deaths; 67.8% involved opioids (ie, 5 per 100,000 population represent prescription opioids).16
The VHA is committed to reducing opioid use and veteran suicide prevention. In 2013 the VHA launched the Opioid Safety Initiative employing 4 strategies: education, pain management, risk management, and addiction treatment.17 To address the opioid epidemic, the North Florida/South Georgia Veteran Health System (NF/SGVHS) developed and implemented a multispecialty Opioid Risk Reduction Program that is fully integrated with mental health and addiction services. The purpose of the NF/SGVHS one-stop pain addiction clinic is to provide a treatment program for chronic pain and addiction. The program includes elements of a whole health approach to pain care, including battlefield and traditional acupuncture. The focus went beyond replacing pharmacologic treatments with a complementary integrative health approach to helping veterans regain control of their lives through empowerment, skill building, shared goal setting, and reinforcing self-management.
The self-management programs include a pain school for patient education, a pain psychology program, and a yoga program, all stressing self-management offered onsite and via telehealth. Special effort was directed to identify patients with OUD and opioid dependence. Many of these patients were transitioned to buprenorphine, a potent analgesic that suppresses opioid cravings and withdrawal symptoms associated with stopping opioids. The clinic was structured so that patients could be seen often for follow-up and support. In addition, open lines of communication and referral were set up between this clinic, the interventional pain clinic, and the physical medicine and rehabilitation service. A detailed description of this program has been published elsewhere.18
The number of veterans receiving opioid prescription across the VHA system decreased by 172,000 prescriptions quarterly between 2012 and 2016.19 Fewer veterans were prescribed high doses of opioids or concomitant interacting medicines and more veterans were receiving nonopioid therapies.19 The prescription reduction across the VHA has varied. For example, from 2012 to 2017 the NF/SGVHS reported an 87% reduction of opioid prescriptions (≥ 100 mg morphine equivalents/d), compared with the VHA national average reduction of 49%.18
Vigorous opioid reduction is controversial. In a systematic review on opioid reduction, Frank and colleagues reported some beneficial effects of opioid reduction, such as increased health-related quality of life.20 However, another study suggested a risk of increased pain with opioid tapering.21 The literature findings on the association between prescription opioid use and suicide are mixed. The VHA Office of Mental Health and Suicide Prevention literature review reported that veterans were at increased risk of committing suicide within the first 6 months of discontinuing opioid therapy.22 Another study reported that veterans who discontinued long-term opioid treatment had an increased risk for suicidal ideation.23 However, higher doses of opioids were associated with an increased risk for suicide among individuals with chronic pain.10 The link between opioid tapering and the risk of suicide or overdose is uncertain.
Bohnert and Ilgen suggested that discontinuing prescription opioids leads to suicide without examining the risk factors that influenced discontinuation is ill-informed.7 Strong evidence about the association or relationship among opioid use, overdose, and suicide is needed. To increase our understanding of that association, Bohnert and Ilgen argued for multifaceted interventions that simultaneously address the shared causes and risk factors for OUD,7 such as the multispecialty Opioid Risk Reduction Program at NF/SGVHS.
Because of the reported association between robust integrated mental health and addiction, primary care pain clinic intervention, and the higher rate of opioid tapering in NF/SGVHS,18 this study aims to describe the pattern of overdose diagnosis (opioid overdose and nonopioid overdose) and pattern of suicide rates among veterans enrolled in NF/SGVHS, Veterans Integrated Service Network (VISN) 8, and the entire VA health care system during 2012 to 2016.The study reviewed and compared overdose diagnosis and suicide rates among veterans across NF/SGVHS and 2 other levels of the VA health care system to determine whether there were variances in the pattern of overdose/suicide rates and to explore these differences.
Methods
In this retrospective study, aggregate data were obtained from several sources. First, the drug overdose data were extracted from the VA Support Service Center (VSSC) medical diagnosis cube. We reviewed the literature for opioid codes reported in the literature and compared these reported opioid International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, 10th Revision (ICD-10) codes with the local facility patient-level comprehensive overdose diagnosis codes. Based on the comparison, we found 98 ICD-9 and ICD-10 overdose diagnosis codes and ran the modified codes against the VSSC national database. Overdose data were aggregated by facility and fiscal year, and the overdose rates (per 1,000) were calculated for unique veteran users at the 3 levels (NF/SGVHS, VISN 8, and VA national) as the denominator.
Each of the 18 VISNs comprise multiple VAMCs and clinics within a geographic region. VISN 8 encompasses most of Florida and portions of southern Georgia and the Caribbean (Puerto Rico, US Virgin Islands), including NF/SGVHS.
In this study, drug overdose refers to the overdose or poisoning from all drugs (ie, opioids, cocaine, amphetamines, sedatives, etc) and defined as any unintentional (accidental), deliberate, or intent undetermined drug poisoning.24 The suicide data for this study were drawn from the VA Suicide Prevention Program at 3 different levels: NF/SGVHS, VISN 8, and VHA national. Suicide is death caused by an intentional act of injuring oneself with the intent to die.25
This descriptive study compared the rate of annual drug overdoses (per 1,000 enrollees) between NF/SGVHS, VISN 8, and VHA national from 2012 to 2016. It also compared the annual rate of suicide per 100,000 enrollees across these 3 levels of the VHA. The overdose and suicide rates and numbers are mutually exclusive, meaning the VISN 8 data do not include the NF/SGVHS information, and the national data excluded data from VISN 8 and NF/SGVHS. This approach helped improve the quality of multiple level comparisons for different levels of the VHA system.
Results
Figure 1 shows the pattern of overdose diagnosis by rates (per 1,000) across the study period (2012 to 2016) and compares patterns at 3 levels of VHA (NF/SGVHS, VISN 8, and VHA national). The average annual rate of overdose diagnoses for NF/SGVHS during the study was slightly higher (16.8 per 1,000) than that of VISN 8 (16 per 1,000) and VHA national (15.3 per 1,000), but by the end of the study period the NF/SGVHS rate (18.6 per 1,000) nearly matched the national rate (18.2 per 1,000) and was lower than the VISN 8 rate (20.4 per 1,000). Additionally, NF/SGVHS had less variability (SD, 1.34) in yearly average overdose rates compared with VISN 8 (SD, 2.96), and VHA national (SD, 1.69).
From 2013 to 2014 the overdose diagnosis rate for NF/SGVHS remained the same (17.1 per 1,000). A similar pattern was observed for the VHA national data, whereas the VISN 8 data showed a steady increase during the same period. In 2015, the NF/SGVHS had 0.7 per 1,000 decrease in overdose diagnosis rate, whereas VISN 8 and VHA national data showed 1.7 per 1,000 and 0.9 per 1,000 increases, respectively. During the last year of the study (2016), there was a dramatic increase in overdose diagnosis for all the health care systems, ranging from 2.2 per 1,000 for NF/SGVHS to 3.3 per 1,000 for VISN 8.
Figure 2 shows the annual rates (per 100,000 individuals) of suicide for NF/SGVHS, VISN 8, and VHA national. The suicide pattern for VISN 8 shows a cyclical acceleration and deceleration trend across the study period. From 2012 to 2014, the VHA national data show a steady increase of about 1 per 100,000 from year to year. On the contrary, NF/SGVHS shows a low suicide rate from year to year within the same period with a rate of 10 per 100,000 in 2013 compared with the previous year. Although the NF/SGVHS suicide rate increased in 2016 (10.4 per 100,000), it remained lower than that of VISN 8 (10.7 per 100,00) and VHA national (38.2 per 100,000).
This study shows that NF/SGVHS had the lowest average annual rate of suicide (9.1 per 100,000) during the study period, which was 4 times lower than that of VHA national and 2.6 times lower than VISN 8.
Discussion
This study described and compared the distribution pattern of overdose (nonopioid and opioid) and suicide rates at different levels of the VHA system. Although VHA implemented systemwide opioid tapering in 2013, little is known about the association between opioid tapering and overdose and suicide. We believe a retrospective examination regarding overdose and suicide among VHA users at 3 different levels of the system from 2012 to 2016 could contribute to the discussion regarding the potential risks and benefits of discontinuing opioids.
First, the average annual rate of overdose diagnosis for NF/SGVHS during the study period was slightly higher (16.8 per 1,000) compared with those of VISN 8 (16.0 per 1,000) and VHA national (15.3 per 1,000) with a general pattern of increase and minimum variations in the rates observed during the study period among the 3 levels of the system. These increased overdose patterns are consistent with other reports in the literature.14 By the end of the study period, the NF/SGVHS rate (18.6 per 1,000) nearly matched the national rate (18.2 per 1,000) and was lower than VISN 8 (20.4 per 1,000). During the last year of the study period (2016), there was a dramatic increase in overdose diagnosis for all health care systems ranging from 2.2 per 1,000 for NF/SGVHS to 3.3 per 1,000 for VISN 8, which might be because of the VHA systemwide change of diagnosis code from ICD-9 to ICD-10, which includes more detailed diagnosis codes.
Second, our results showed that NF/SGVHS had the lowest average annual suicide rate (9.1 per 100,000) during the study period, which is one-fourth the VHA national rate and 2.6 per 100,000 lower than the VISN 8 rate. According to Bohnert and Ilgen,programs that improve the quality of pain care, expand access to psychotherapy, and increase access to medication-assisted treatment for OUDs could reduce suicide by drug overdose.7 We suggest that the low suicide rate at NF/SGVHS and the difference in the suicide rates between the NF/SGVHS and VISN 8 and VHA national data might be associated with the practice-based biopsychosocial interventions implemented at NF/SGVHS.
Our data showed a rise in the incidence of suicide at the NF/SGVHS in 2016. We are not aware of a local change in conditions, policy, and practice that would account for this increase. Suicide is variable, and data are likely to show spikes and valleys. Based on the available data, although the incidence of suicides at the NF/SGVHS in 2016 was higher, it remained below the VISN 8 and national VHA rate. This study seems to support the practice of tapering or stopping opioids within the context of a multidisciplinary approach that offers frequent follow-up, nonopioid options, and treatment of opioid addiction/dependence.
Limitations
The research findings of this study are limited by the retrospective and descriptive nature of its design. However, the findings might provide important information for understanding variations of overdose and suicide among VHA enrollees. Studies that use more robust methodologies are warranted to clinically investigate the impact of a multispecialty opioid risk reduction program targeting chronic pain and addiction management and identify best practices of opioid reduction and any unintended consequences that might arise from opioid tapering.26 Further, we did not have access to the VA national overdose and suicide data after 2016. Similar to most retrospective data studies, ours might be limited by availability of national overdose and suicide data after 2016. It is important for future studies to cross-validate our study findings.
Conclusions
The NF/SGVHS developed and implemented a biopsychosocial model of pain treatment that includes multicomponent primary care integrated with mental health and addiction services as well as the interventional pain and physical medicine and rehabilitation services. The presence of this program, during a period when the facility was tapering opioids is likely to account for at least part of the relative reduction in suicide.
1. American Foundation for Suicide Prevention. Suicide statistics. https://afsp.org/about-suicide/suicide-statistics. Updated 2019. Accessed September 2, 2020.
2. Shane L 3rd. New veteran suicide numbers raise concerns among experts hoping for positive news. https://www.militarytimes.com/news/pentagon-congress/2019/10/09/new-veteran-suicide-numbers-raise-concerns-among-experts-hoping-for-positive-news. Published October 9, 2019. Accessed July 23, 2020.
3. Veterans Health Administration, Office of Mental Health and Suicide Prevention. Veteran suicide data report, 2005–2017. https://www.mentalhealth.va.gov/docs/data-sheets/2019/2019_National_Veteran_Suicide_Prevention_Annual_Report_508.pdf. Published September 2019. Accessed July 20, 2020.
4. Gallagher RM. Advancing the pain agenda in the veteran population. Anesthesiol Clin. 2016;34(2):357-378. doi:10.1016/j.anclin.2016.01.003
5. Ilgen MA, Kleinberg F, Ignacio RV, et al. Noncancer pain conditions and risk of suicide. JAMA Psychiatry. 2013;70(7):692-697. doi:10.1001/jamapsychiatry.2013.908
6. Frenk SM, Porter KS, Paulozzi LJ. Prescription opioid analgesic use among adults: United States, 1999-2012. National Center for Health Statistics data brief. https://www.cdc.gov/nchs/products/databriefs/db189.htm. Published February 25, 2015. Accessed July 20, 2020.
7. Bohnert ASB, Ilgen MA. Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019;380(14):71-79. doi:10.1056/NEJMc1901540
8. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152(2):85-92. doi:10.7326/0003-4819-152-2-201001190-00006
9. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686-691. doi:10.1001/archinternmed.2011.117
10. Ilgen MA, Bohnert AS, Ganoczy D, Bair MJ, McCarthy JF, Blow FC. Opioid dose and risk of suicide. Pain. 2016;157(5):1079-1084. doi:10.1097/j.pain.0000000000000484
11. Sinyor M, Howlett A, Cheung AH, Schaffer A. Substances used in completed suicide by overdose in Toronto: an observational study of coroner’s data. Can J Psychiatry. 2012;57(3):184-191. doi:10.1177/070674371205700308
12. Wilcox HC, Conner KR, Caine ED. Association of alcohol and drug use disorders and completed suicide: an empirical review of cohort studies. Drug Alcohol Depend. 2004;76(suppl):S11-S19 doi:10.1016/j.drugalcdep.2004.08.003.
13. Baser OL, Mardekian XJ, Schaaf D, Wang L, Joshi AV. Prevalence of diagnosed opioid abuse and its economic burden in the Veterans Health Administration. Pain Pract. 2014;14(5):437-445. doi:10.1111/papr.12097
14. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the united states, 1999-2015. National Center for Health Statistics data brief. https://www.cdc.gov/nchs/data/databriefs/db273.pdf. Published February 2017. Accessed July 20, 2020.
15. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. doi:10.15585/mmwr.mm655051e1
16. Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and opioid-involved overdose deaths—United States, 2013-2017. MMWR Morb Mortal Wkly Rep. 2019,67(5152):1419-1427. doi:10.15585/mmwr.mm675152e1
17. US Department of Veterans Affairs and Department of Defense. VA/DOD clinical practice guideline for opioid therapy for chronic pain version 3.0. https://www.healthquality.va.gov/guidelines/pain/cot. Updated March 1, 2018. Accessed July 20, 2020.
18. Vaughn IA, Beyth RJ, Ayers ML, et al. Multispecialty opioid risk reduction program targeting chronic pain and addiction management in veterans. Fed Pract. 2019;36(9):406-411.
19. Gellad WF, Good CB, Shulkin DJ. Addressing the opioid epidemic in the United States: lessons from the Department of Veterans Affairs. JAMA Intern Med. 2017;177(5):611-612. doi:10.1001/jamainternmed.2017.0147
20. Frank JW, Lovejoy TI, Becker WC, et al. Patient outcomes in dose reduction or discontinuation of long-term opioid therapy: a systematic review. Ann Intern Med. 2017;167(3):181-191. doi:10.7326/M17-0598
21. Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc. 2015;90(6):828-842. doi:10.1016/j.mayocp.2015.04.003
22. Veterans Health Administration, Office of Mental Health and Suicide Prevention. Opioid use and suicide risk. https://www.mentalhealth.va.gov/suicide_prevention/docs/Literature_Review_Opioid_Use_and_Suicide_Risk_508_FINAL_04-26-2019.pdf. Published April 26, 2019. Accessed July 20, 2020.
23. Demidenko MI, Dobscha SK, Morasco BJ, Meath THA, Ilgen MA, Lovejoy TI. Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. Gen Hosp Psychiatry. 2017;47:29-35. doi:10.1016/j.genhosppsych.2017.04.011
24. National Institute on Drug Abuse. Intentional versus unintentional overdose deaths. https://www.drugabuse.gov/related-topics/treatment/intentional-vs-unintentional-overdose-deaths. Updated February 13, 2017. Accessed July 20, 2020.
25. Centers for Disease Control and Prevention. Preventing suicide. https://www.cdc.gov/violenceprevention/pdf/suicide-factsheet.pdf. Published 2018. Accessed July 20, 2020.
26. Webster LR. Pain and suicide: the other side of the opioid story. Pain Med. 2014;15(3):345-346. doi:10.1111/pme.12398
Suicide is the 10th leading cause of death in the US. In 2017, there were 47,173 deaths by suicide (14 deaths per 100,000 people), representing a 33% increase from 1999.1 In 2017 veterans accounted for 13.5% of all suicide deaths among US adults, although veterans comprised only 7.9% of the adult population; the age- and sex-adjusted suicide rate was 1.5 times higher for veterans than that of nonveteran adults.2,3
Among veteran users of Veterans Health Administration (VHA) services, mental health and substance use disorders, chronic medical conditions, and chronic pain are associated with an increased risk for suicide.3 About one-half of VHA veterans have been diagnosed with chronic pain.4 A chronic pain diagnosis (eg, back pain, migraine, and psychogenic pain) increased the risk of death by suicide even after adjusting for comorbid psychiatric diagnoses, according to a study on pain and suicide among US veterans.5
One-quarter of veterans received an opioid prescription during VHA outpatient care in 2012.4 Increased prescribing of opioid medications has been associated with opioid overdose and suicides.6-10 Opioids are the most common drugs found in suicide by overdose.11 The rate of opioid-related suicide deaths is 13 times higher among individuals with opioid use disorder (OUD) than it is for those without OUD.12 The rate of OUD diagnosis among VHA users was 7 times higher than that for non-VHA users.13
In the US the age-adjusted rate of drug overdose deaths increased from 6 per 100,000 persons in 1999 to 22 per 100,000 in 2017.14 Drug overdoses accounted for 52,404 US deaths in 2015; 33,091 (63.1%) were from opioids.15 In 2017, there were 70,237 drug overdose deaths; 67.8% involved opioids (ie, 5 per 100,000 population represent prescription opioids).16
The VHA is committed to reducing opioid use and veteran suicide prevention. In 2013 the VHA launched the Opioid Safety Initiative employing 4 strategies: education, pain management, risk management, and addiction treatment.17 To address the opioid epidemic, the North Florida/South Georgia Veteran Health System (NF/SGVHS) developed and implemented a multispecialty Opioid Risk Reduction Program that is fully integrated with mental health and addiction services. The purpose of the NF/SGVHS one-stop pain addiction clinic is to provide a treatment program for chronic pain and addiction. The program includes elements of a whole health approach to pain care, including battlefield and traditional acupuncture. The focus went beyond replacing pharmacologic treatments with a complementary integrative health approach to helping veterans regain control of their lives through empowerment, skill building, shared goal setting, and reinforcing self-management.
The self-management programs include a pain school for patient education, a pain psychology program, and a yoga program, all stressing self-management offered onsite and via telehealth. Special effort was directed to identify patients with OUD and opioid dependence. Many of these patients were transitioned to buprenorphine, a potent analgesic that suppresses opioid cravings and withdrawal symptoms associated with stopping opioids. The clinic was structured so that patients could be seen often for follow-up and support. In addition, open lines of communication and referral were set up between this clinic, the interventional pain clinic, and the physical medicine and rehabilitation service. A detailed description of this program has been published elsewhere.18
The number of veterans receiving opioid prescription across the VHA system decreased by 172,000 prescriptions quarterly between 2012 and 2016.19 Fewer veterans were prescribed high doses of opioids or concomitant interacting medicines and more veterans were receiving nonopioid therapies.19 The prescription reduction across the VHA has varied. For example, from 2012 to 2017 the NF/SGVHS reported an 87% reduction of opioid prescriptions (≥ 100 mg morphine equivalents/d), compared with the VHA national average reduction of 49%.18
Vigorous opioid reduction is controversial. In a systematic review on opioid reduction, Frank and colleagues reported some beneficial effects of opioid reduction, such as increased health-related quality of life.20 However, another study suggested a risk of increased pain with opioid tapering.21 The literature findings on the association between prescription opioid use and suicide are mixed. The VHA Office of Mental Health and Suicide Prevention literature review reported that veterans were at increased risk of committing suicide within the first 6 months of discontinuing opioid therapy.22 Another study reported that veterans who discontinued long-term opioid treatment had an increased risk for suicidal ideation.23 However, higher doses of opioids were associated with an increased risk for suicide among individuals with chronic pain.10 The link between opioid tapering and the risk of suicide or overdose is uncertain.
Bohnert and Ilgen suggested that discontinuing prescription opioids leads to suicide without examining the risk factors that influenced discontinuation is ill-informed.7 Strong evidence about the association or relationship among opioid use, overdose, and suicide is needed. To increase our understanding of that association, Bohnert and Ilgen argued for multifaceted interventions that simultaneously address the shared causes and risk factors for OUD,7 such as the multispecialty Opioid Risk Reduction Program at NF/SGVHS.
Because of the reported association between robust integrated mental health and addiction, primary care pain clinic intervention, and the higher rate of opioid tapering in NF/SGVHS,18 this study aims to describe the pattern of overdose diagnosis (opioid overdose and nonopioid overdose) and pattern of suicide rates among veterans enrolled in NF/SGVHS, Veterans Integrated Service Network (VISN) 8, and the entire VA health care system during 2012 to 2016.The study reviewed and compared overdose diagnosis and suicide rates among veterans across NF/SGVHS and 2 other levels of the VA health care system to determine whether there were variances in the pattern of overdose/suicide rates and to explore these differences.
Methods
In this retrospective study, aggregate data were obtained from several sources. First, the drug overdose data were extracted from the VA Support Service Center (VSSC) medical diagnosis cube. We reviewed the literature for opioid codes reported in the literature and compared these reported opioid International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, 10th Revision (ICD-10) codes with the local facility patient-level comprehensive overdose diagnosis codes. Based on the comparison, we found 98 ICD-9 and ICD-10 overdose diagnosis codes and ran the modified codes against the VSSC national database. Overdose data were aggregated by facility and fiscal year, and the overdose rates (per 1,000) were calculated for unique veteran users at the 3 levels (NF/SGVHS, VISN 8, and VA national) as the denominator.
Each of the 18 VISNs comprise multiple VAMCs and clinics within a geographic region. VISN 8 encompasses most of Florida and portions of southern Georgia and the Caribbean (Puerto Rico, US Virgin Islands), including NF/SGVHS.
In this study, drug overdose refers to the overdose or poisoning from all drugs (ie, opioids, cocaine, amphetamines, sedatives, etc) and defined as any unintentional (accidental), deliberate, or intent undetermined drug poisoning.24 The suicide data for this study were drawn from the VA Suicide Prevention Program at 3 different levels: NF/SGVHS, VISN 8, and VHA national. Suicide is death caused by an intentional act of injuring oneself with the intent to die.25
This descriptive study compared the rate of annual drug overdoses (per 1,000 enrollees) between NF/SGVHS, VISN 8, and VHA national from 2012 to 2016. It also compared the annual rate of suicide per 100,000 enrollees across these 3 levels of the VHA. The overdose and suicide rates and numbers are mutually exclusive, meaning the VISN 8 data do not include the NF/SGVHS information, and the national data excluded data from VISN 8 and NF/SGVHS. This approach helped improve the quality of multiple level comparisons for different levels of the VHA system.
Results
Figure 1 shows the pattern of overdose diagnosis by rates (per 1,000) across the study period (2012 to 2016) and compares patterns at 3 levels of VHA (NF/SGVHS, VISN 8, and VHA national). The average annual rate of overdose diagnoses for NF/SGVHS during the study was slightly higher (16.8 per 1,000) than that of VISN 8 (16 per 1,000) and VHA national (15.3 per 1,000), but by the end of the study period the NF/SGVHS rate (18.6 per 1,000) nearly matched the national rate (18.2 per 1,000) and was lower than the VISN 8 rate (20.4 per 1,000). Additionally, NF/SGVHS had less variability (SD, 1.34) in yearly average overdose rates compared with VISN 8 (SD, 2.96), and VHA national (SD, 1.69).
From 2013 to 2014 the overdose diagnosis rate for NF/SGVHS remained the same (17.1 per 1,000). A similar pattern was observed for the VHA national data, whereas the VISN 8 data showed a steady increase during the same period. In 2015, the NF/SGVHS had 0.7 per 1,000 decrease in overdose diagnosis rate, whereas VISN 8 and VHA national data showed 1.7 per 1,000 and 0.9 per 1,000 increases, respectively. During the last year of the study (2016), there was a dramatic increase in overdose diagnosis for all the health care systems, ranging from 2.2 per 1,000 for NF/SGVHS to 3.3 per 1,000 for VISN 8.
Figure 2 shows the annual rates (per 100,000 individuals) of suicide for NF/SGVHS, VISN 8, and VHA national. The suicide pattern for VISN 8 shows a cyclical acceleration and deceleration trend across the study period. From 2012 to 2014, the VHA national data show a steady increase of about 1 per 100,000 from year to year. On the contrary, NF/SGVHS shows a low suicide rate from year to year within the same period with a rate of 10 per 100,000 in 2013 compared with the previous year. Although the NF/SGVHS suicide rate increased in 2016 (10.4 per 100,000), it remained lower than that of VISN 8 (10.7 per 100,00) and VHA national (38.2 per 100,000).
This study shows that NF/SGVHS had the lowest average annual rate of suicide (9.1 per 100,000) during the study period, which was 4 times lower than that of VHA national and 2.6 times lower than VISN 8.
Discussion
This study described and compared the distribution pattern of overdose (nonopioid and opioid) and suicide rates at different levels of the VHA system. Although VHA implemented systemwide opioid tapering in 2013, little is known about the association between opioid tapering and overdose and suicide. We believe a retrospective examination regarding overdose and suicide among VHA users at 3 different levels of the system from 2012 to 2016 could contribute to the discussion regarding the potential risks and benefits of discontinuing opioids.
First, the average annual rate of overdose diagnosis for NF/SGVHS during the study period was slightly higher (16.8 per 1,000) compared with those of VISN 8 (16.0 per 1,000) and VHA national (15.3 per 1,000) with a general pattern of increase and minimum variations in the rates observed during the study period among the 3 levels of the system. These increased overdose patterns are consistent with other reports in the literature.14 By the end of the study period, the NF/SGVHS rate (18.6 per 1,000) nearly matched the national rate (18.2 per 1,000) and was lower than VISN 8 (20.4 per 1,000). During the last year of the study period (2016), there was a dramatic increase in overdose diagnosis for all health care systems ranging from 2.2 per 1,000 for NF/SGVHS to 3.3 per 1,000 for VISN 8, which might be because of the VHA systemwide change of diagnosis code from ICD-9 to ICD-10, which includes more detailed diagnosis codes.
Second, our results showed that NF/SGVHS had the lowest average annual suicide rate (9.1 per 100,000) during the study period, which is one-fourth the VHA national rate and 2.6 per 100,000 lower than the VISN 8 rate. According to Bohnert and Ilgen,programs that improve the quality of pain care, expand access to psychotherapy, and increase access to medication-assisted treatment for OUDs could reduce suicide by drug overdose.7 We suggest that the low suicide rate at NF/SGVHS and the difference in the suicide rates between the NF/SGVHS and VISN 8 and VHA national data might be associated with the practice-based biopsychosocial interventions implemented at NF/SGVHS.
Our data showed a rise in the incidence of suicide at the NF/SGVHS in 2016. We are not aware of a local change in conditions, policy, and practice that would account for this increase. Suicide is variable, and data are likely to show spikes and valleys. Based on the available data, although the incidence of suicides at the NF/SGVHS in 2016 was higher, it remained below the VISN 8 and national VHA rate. This study seems to support the practice of tapering or stopping opioids within the context of a multidisciplinary approach that offers frequent follow-up, nonopioid options, and treatment of opioid addiction/dependence.
Limitations
The research findings of this study are limited by the retrospective and descriptive nature of its design. However, the findings might provide important information for understanding variations of overdose and suicide among VHA enrollees. Studies that use more robust methodologies are warranted to clinically investigate the impact of a multispecialty opioid risk reduction program targeting chronic pain and addiction management and identify best practices of opioid reduction and any unintended consequences that might arise from opioid tapering.26 Further, we did not have access to the VA national overdose and suicide data after 2016. Similar to most retrospective data studies, ours might be limited by availability of national overdose and suicide data after 2016. It is important for future studies to cross-validate our study findings.
Conclusions
The NF/SGVHS developed and implemented a biopsychosocial model of pain treatment that includes multicomponent primary care integrated with mental health and addiction services as well as the interventional pain and physical medicine and rehabilitation services. The presence of this program, during a period when the facility was tapering opioids is likely to account for at least part of the relative reduction in suicide.
Suicide is the 10th leading cause of death in the US. In 2017, there were 47,173 deaths by suicide (14 deaths per 100,000 people), representing a 33% increase from 1999.1 In 2017 veterans accounted for 13.5% of all suicide deaths among US adults, although veterans comprised only 7.9% of the adult population; the age- and sex-adjusted suicide rate was 1.5 times higher for veterans than that of nonveteran adults.2,3
Among veteran users of Veterans Health Administration (VHA) services, mental health and substance use disorders, chronic medical conditions, and chronic pain are associated with an increased risk for suicide.3 About one-half of VHA veterans have been diagnosed with chronic pain.4 A chronic pain diagnosis (eg, back pain, migraine, and psychogenic pain) increased the risk of death by suicide even after adjusting for comorbid psychiatric diagnoses, according to a study on pain and suicide among US veterans.5
One-quarter of veterans received an opioid prescription during VHA outpatient care in 2012.4 Increased prescribing of opioid medications has been associated with opioid overdose and suicides.6-10 Opioids are the most common drugs found in suicide by overdose.11 The rate of opioid-related suicide deaths is 13 times higher among individuals with opioid use disorder (OUD) than it is for those without OUD.12 The rate of OUD diagnosis among VHA users was 7 times higher than that for non-VHA users.13
In the US the age-adjusted rate of drug overdose deaths increased from 6 per 100,000 persons in 1999 to 22 per 100,000 in 2017.14 Drug overdoses accounted for 52,404 US deaths in 2015; 33,091 (63.1%) were from opioids.15 In 2017, there were 70,237 drug overdose deaths; 67.8% involved opioids (ie, 5 per 100,000 population represent prescription opioids).16
The VHA is committed to reducing opioid use and veteran suicide prevention. In 2013 the VHA launched the Opioid Safety Initiative employing 4 strategies: education, pain management, risk management, and addiction treatment.17 To address the opioid epidemic, the North Florida/South Georgia Veteran Health System (NF/SGVHS) developed and implemented a multispecialty Opioid Risk Reduction Program that is fully integrated with mental health and addiction services. The purpose of the NF/SGVHS one-stop pain addiction clinic is to provide a treatment program for chronic pain and addiction. The program includes elements of a whole health approach to pain care, including battlefield and traditional acupuncture. The focus went beyond replacing pharmacologic treatments with a complementary integrative health approach to helping veterans regain control of their lives through empowerment, skill building, shared goal setting, and reinforcing self-management.
The self-management programs include a pain school for patient education, a pain psychology program, and a yoga program, all stressing self-management offered onsite and via telehealth. Special effort was directed to identify patients with OUD and opioid dependence. Many of these patients were transitioned to buprenorphine, a potent analgesic that suppresses opioid cravings and withdrawal symptoms associated with stopping opioids. The clinic was structured so that patients could be seen often for follow-up and support. In addition, open lines of communication and referral were set up between this clinic, the interventional pain clinic, and the physical medicine and rehabilitation service. A detailed description of this program has been published elsewhere.18
The number of veterans receiving opioid prescription across the VHA system decreased by 172,000 prescriptions quarterly between 2012 and 2016.19 Fewer veterans were prescribed high doses of opioids or concomitant interacting medicines and more veterans were receiving nonopioid therapies.19 The prescription reduction across the VHA has varied. For example, from 2012 to 2017 the NF/SGVHS reported an 87% reduction of opioid prescriptions (≥ 100 mg morphine equivalents/d), compared with the VHA national average reduction of 49%.18
Vigorous opioid reduction is controversial. In a systematic review on opioid reduction, Frank and colleagues reported some beneficial effects of opioid reduction, such as increased health-related quality of life.20 However, another study suggested a risk of increased pain with opioid tapering.21 The literature findings on the association between prescription opioid use and suicide are mixed. The VHA Office of Mental Health and Suicide Prevention literature review reported that veterans were at increased risk of committing suicide within the first 6 months of discontinuing opioid therapy.22 Another study reported that veterans who discontinued long-term opioid treatment had an increased risk for suicidal ideation.23 However, higher doses of opioids were associated with an increased risk for suicide among individuals with chronic pain.10 The link between opioid tapering and the risk of suicide or overdose is uncertain.
Bohnert and Ilgen suggested that discontinuing prescription opioids leads to suicide without examining the risk factors that influenced discontinuation is ill-informed.7 Strong evidence about the association or relationship among opioid use, overdose, and suicide is needed. To increase our understanding of that association, Bohnert and Ilgen argued for multifaceted interventions that simultaneously address the shared causes and risk factors for OUD,7 such as the multispecialty Opioid Risk Reduction Program at NF/SGVHS.
Because of the reported association between robust integrated mental health and addiction, primary care pain clinic intervention, and the higher rate of opioid tapering in NF/SGVHS,18 this study aims to describe the pattern of overdose diagnosis (opioid overdose and nonopioid overdose) and pattern of suicide rates among veterans enrolled in NF/SGVHS, Veterans Integrated Service Network (VISN) 8, and the entire VA health care system during 2012 to 2016.The study reviewed and compared overdose diagnosis and suicide rates among veterans across NF/SGVHS and 2 other levels of the VA health care system to determine whether there were variances in the pattern of overdose/suicide rates and to explore these differences.
Methods
In this retrospective study, aggregate data were obtained from several sources. First, the drug overdose data were extracted from the VA Support Service Center (VSSC) medical diagnosis cube. We reviewed the literature for opioid codes reported in the literature and compared these reported opioid International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, 10th Revision (ICD-10) codes with the local facility patient-level comprehensive overdose diagnosis codes. Based on the comparison, we found 98 ICD-9 and ICD-10 overdose diagnosis codes and ran the modified codes against the VSSC national database. Overdose data were aggregated by facility and fiscal year, and the overdose rates (per 1,000) were calculated for unique veteran users at the 3 levels (NF/SGVHS, VISN 8, and VA national) as the denominator.
Each of the 18 VISNs comprise multiple VAMCs and clinics within a geographic region. VISN 8 encompasses most of Florida and portions of southern Georgia and the Caribbean (Puerto Rico, US Virgin Islands), including NF/SGVHS.
In this study, drug overdose refers to the overdose or poisoning from all drugs (ie, opioids, cocaine, amphetamines, sedatives, etc) and defined as any unintentional (accidental), deliberate, or intent undetermined drug poisoning.24 The suicide data for this study were drawn from the VA Suicide Prevention Program at 3 different levels: NF/SGVHS, VISN 8, and VHA national. Suicide is death caused by an intentional act of injuring oneself with the intent to die.25
This descriptive study compared the rate of annual drug overdoses (per 1,000 enrollees) between NF/SGVHS, VISN 8, and VHA national from 2012 to 2016. It also compared the annual rate of suicide per 100,000 enrollees across these 3 levels of the VHA. The overdose and suicide rates and numbers are mutually exclusive, meaning the VISN 8 data do not include the NF/SGVHS information, and the national data excluded data from VISN 8 and NF/SGVHS. This approach helped improve the quality of multiple level comparisons for different levels of the VHA system.
Results
Figure 1 shows the pattern of overdose diagnosis by rates (per 1,000) across the study period (2012 to 2016) and compares patterns at 3 levels of VHA (NF/SGVHS, VISN 8, and VHA national). The average annual rate of overdose diagnoses for NF/SGVHS during the study was slightly higher (16.8 per 1,000) than that of VISN 8 (16 per 1,000) and VHA national (15.3 per 1,000), but by the end of the study period the NF/SGVHS rate (18.6 per 1,000) nearly matched the national rate (18.2 per 1,000) and was lower than the VISN 8 rate (20.4 per 1,000). Additionally, NF/SGVHS had less variability (SD, 1.34) in yearly average overdose rates compared with VISN 8 (SD, 2.96), and VHA national (SD, 1.69).
From 2013 to 2014 the overdose diagnosis rate for NF/SGVHS remained the same (17.1 per 1,000). A similar pattern was observed for the VHA national data, whereas the VISN 8 data showed a steady increase during the same period. In 2015, the NF/SGVHS had 0.7 per 1,000 decrease in overdose diagnosis rate, whereas VISN 8 and VHA national data showed 1.7 per 1,000 and 0.9 per 1,000 increases, respectively. During the last year of the study (2016), there was a dramatic increase in overdose diagnosis for all the health care systems, ranging from 2.2 per 1,000 for NF/SGVHS to 3.3 per 1,000 for VISN 8.
Figure 2 shows the annual rates (per 100,000 individuals) of suicide for NF/SGVHS, VISN 8, and VHA national. The suicide pattern for VISN 8 shows a cyclical acceleration and deceleration trend across the study period. From 2012 to 2014, the VHA national data show a steady increase of about 1 per 100,000 from year to year. On the contrary, NF/SGVHS shows a low suicide rate from year to year within the same period with a rate of 10 per 100,000 in 2013 compared with the previous year. Although the NF/SGVHS suicide rate increased in 2016 (10.4 per 100,000), it remained lower than that of VISN 8 (10.7 per 100,00) and VHA national (38.2 per 100,000).
This study shows that NF/SGVHS had the lowest average annual rate of suicide (9.1 per 100,000) during the study period, which was 4 times lower than that of VHA national and 2.6 times lower than VISN 8.
Discussion
This study described and compared the distribution pattern of overdose (nonopioid and opioid) and suicide rates at different levels of the VHA system. Although VHA implemented systemwide opioid tapering in 2013, little is known about the association between opioid tapering and overdose and suicide. We believe a retrospective examination regarding overdose and suicide among VHA users at 3 different levels of the system from 2012 to 2016 could contribute to the discussion regarding the potential risks and benefits of discontinuing opioids.
First, the average annual rate of overdose diagnosis for NF/SGVHS during the study period was slightly higher (16.8 per 1,000) compared with those of VISN 8 (16.0 per 1,000) and VHA national (15.3 per 1,000) with a general pattern of increase and minimum variations in the rates observed during the study period among the 3 levels of the system. These increased overdose patterns are consistent with other reports in the literature.14 By the end of the study period, the NF/SGVHS rate (18.6 per 1,000) nearly matched the national rate (18.2 per 1,000) and was lower than VISN 8 (20.4 per 1,000). During the last year of the study period (2016), there was a dramatic increase in overdose diagnosis for all health care systems ranging from 2.2 per 1,000 for NF/SGVHS to 3.3 per 1,000 for VISN 8, which might be because of the VHA systemwide change of diagnosis code from ICD-9 to ICD-10, which includes more detailed diagnosis codes.
Second, our results showed that NF/SGVHS had the lowest average annual suicide rate (9.1 per 100,000) during the study period, which is one-fourth the VHA national rate and 2.6 per 100,000 lower than the VISN 8 rate. According to Bohnert and Ilgen,programs that improve the quality of pain care, expand access to psychotherapy, and increase access to medication-assisted treatment for OUDs could reduce suicide by drug overdose.7 We suggest that the low suicide rate at NF/SGVHS and the difference in the suicide rates between the NF/SGVHS and VISN 8 and VHA national data might be associated with the practice-based biopsychosocial interventions implemented at NF/SGVHS.
Our data showed a rise in the incidence of suicide at the NF/SGVHS in 2016. We are not aware of a local change in conditions, policy, and practice that would account for this increase. Suicide is variable, and data are likely to show spikes and valleys. Based on the available data, although the incidence of suicides at the NF/SGVHS in 2016 was higher, it remained below the VISN 8 and national VHA rate. This study seems to support the practice of tapering or stopping opioids within the context of a multidisciplinary approach that offers frequent follow-up, nonopioid options, and treatment of opioid addiction/dependence.
Limitations
The research findings of this study are limited by the retrospective and descriptive nature of its design. However, the findings might provide important information for understanding variations of overdose and suicide among VHA enrollees. Studies that use more robust methodologies are warranted to clinically investigate the impact of a multispecialty opioid risk reduction program targeting chronic pain and addiction management and identify best practices of opioid reduction and any unintended consequences that might arise from opioid tapering.26 Further, we did not have access to the VA national overdose and suicide data after 2016. Similar to most retrospective data studies, ours might be limited by availability of national overdose and suicide data after 2016. It is important for future studies to cross-validate our study findings.
Conclusions
The NF/SGVHS developed and implemented a biopsychosocial model of pain treatment that includes multicomponent primary care integrated with mental health and addiction services as well as the interventional pain and physical medicine and rehabilitation services. The presence of this program, during a period when the facility was tapering opioids is likely to account for at least part of the relative reduction in suicide.
1. American Foundation for Suicide Prevention. Suicide statistics. https://afsp.org/about-suicide/suicide-statistics. Updated 2019. Accessed September 2, 2020.
2. Shane L 3rd. New veteran suicide numbers raise concerns among experts hoping for positive news. https://www.militarytimes.com/news/pentagon-congress/2019/10/09/new-veteran-suicide-numbers-raise-concerns-among-experts-hoping-for-positive-news. Published October 9, 2019. Accessed July 23, 2020.
3. Veterans Health Administration, Office of Mental Health and Suicide Prevention. Veteran suicide data report, 2005–2017. https://www.mentalhealth.va.gov/docs/data-sheets/2019/2019_National_Veteran_Suicide_Prevention_Annual_Report_508.pdf. Published September 2019. Accessed July 20, 2020.
4. Gallagher RM. Advancing the pain agenda in the veteran population. Anesthesiol Clin. 2016;34(2):357-378. doi:10.1016/j.anclin.2016.01.003
5. Ilgen MA, Kleinberg F, Ignacio RV, et al. Noncancer pain conditions and risk of suicide. JAMA Psychiatry. 2013;70(7):692-697. doi:10.1001/jamapsychiatry.2013.908
6. Frenk SM, Porter KS, Paulozzi LJ. Prescription opioid analgesic use among adults: United States, 1999-2012. National Center for Health Statistics data brief. https://www.cdc.gov/nchs/products/databriefs/db189.htm. Published February 25, 2015. Accessed July 20, 2020.
7. Bohnert ASB, Ilgen MA. Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019;380(14):71-79. doi:10.1056/NEJMc1901540
8. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152(2):85-92. doi:10.7326/0003-4819-152-2-201001190-00006
9. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686-691. doi:10.1001/archinternmed.2011.117
10. Ilgen MA, Bohnert AS, Ganoczy D, Bair MJ, McCarthy JF, Blow FC. Opioid dose and risk of suicide. Pain. 2016;157(5):1079-1084. doi:10.1097/j.pain.0000000000000484
11. Sinyor M, Howlett A, Cheung AH, Schaffer A. Substances used in completed suicide by overdose in Toronto: an observational study of coroner’s data. Can J Psychiatry. 2012;57(3):184-191. doi:10.1177/070674371205700308
12. Wilcox HC, Conner KR, Caine ED. Association of alcohol and drug use disorders and completed suicide: an empirical review of cohort studies. Drug Alcohol Depend. 2004;76(suppl):S11-S19 doi:10.1016/j.drugalcdep.2004.08.003.
13. Baser OL, Mardekian XJ, Schaaf D, Wang L, Joshi AV. Prevalence of diagnosed opioid abuse and its economic burden in the Veterans Health Administration. Pain Pract. 2014;14(5):437-445. doi:10.1111/papr.12097
14. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the united states, 1999-2015. National Center for Health Statistics data brief. https://www.cdc.gov/nchs/data/databriefs/db273.pdf. Published February 2017. Accessed July 20, 2020.
15. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. doi:10.15585/mmwr.mm655051e1
16. Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and opioid-involved overdose deaths—United States, 2013-2017. MMWR Morb Mortal Wkly Rep. 2019,67(5152):1419-1427. doi:10.15585/mmwr.mm675152e1
17. US Department of Veterans Affairs and Department of Defense. VA/DOD clinical practice guideline for opioid therapy for chronic pain version 3.0. https://www.healthquality.va.gov/guidelines/pain/cot. Updated March 1, 2018. Accessed July 20, 2020.
18. Vaughn IA, Beyth RJ, Ayers ML, et al. Multispecialty opioid risk reduction program targeting chronic pain and addiction management in veterans. Fed Pract. 2019;36(9):406-411.
19. Gellad WF, Good CB, Shulkin DJ. Addressing the opioid epidemic in the United States: lessons from the Department of Veterans Affairs. JAMA Intern Med. 2017;177(5):611-612. doi:10.1001/jamainternmed.2017.0147
20. Frank JW, Lovejoy TI, Becker WC, et al. Patient outcomes in dose reduction or discontinuation of long-term opioid therapy: a systematic review. Ann Intern Med. 2017;167(3):181-191. doi:10.7326/M17-0598
21. Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc. 2015;90(6):828-842. doi:10.1016/j.mayocp.2015.04.003
22. Veterans Health Administration, Office of Mental Health and Suicide Prevention. Opioid use and suicide risk. https://www.mentalhealth.va.gov/suicide_prevention/docs/Literature_Review_Opioid_Use_and_Suicide_Risk_508_FINAL_04-26-2019.pdf. Published April 26, 2019. Accessed July 20, 2020.
23. Demidenko MI, Dobscha SK, Morasco BJ, Meath THA, Ilgen MA, Lovejoy TI. Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. Gen Hosp Psychiatry. 2017;47:29-35. doi:10.1016/j.genhosppsych.2017.04.011
24. National Institute on Drug Abuse. Intentional versus unintentional overdose deaths. https://www.drugabuse.gov/related-topics/treatment/intentional-vs-unintentional-overdose-deaths. Updated February 13, 2017. Accessed July 20, 2020.
25. Centers for Disease Control and Prevention. Preventing suicide. https://www.cdc.gov/violenceprevention/pdf/suicide-factsheet.pdf. Published 2018. Accessed July 20, 2020.
26. Webster LR. Pain and suicide: the other side of the opioid story. Pain Med. 2014;15(3):345-346. doi:10.1111/pme.12398
1. American Foundation for Suicide Prevention. Suicide statistics. https://afsp.org/about-suicide/suicide-statistics. Updated 2019. Accessed September 2, 2020.
2. Shane L 3rd. New veteran suicide numbers raise concerns among experts hoping for positive news. https://www.militarytimes.com/news/pentagon-congress/2019/10/09/new-veteran-suicide-numbers-raise-concerns-among-experts-hoping-for-positive-news. Published October 9, 2019. Accessed July 23, 2020.
3. Veterans Health Administration, Office of Mental Health and Suicide Prevention. Veteran suicide data report, 2005–2017. https://www.mentalhealth.va.gov/docs/data-sheets/2019/2019_National_Veteran_Suicide_Prevention_Annual_Report_508.pdf. Published September 2019. Accessed July 20, 2020.
4. Gallagher RM. Advancing the pain agenda in the veteran population. Anesthesiol Clin. 2016;34(2):357-378. doi:10.1016/j.anclin.2016.01.003
5. Ilgen MA, Kleinberg F, Ignacio RV, et al. Noncancer pain conditions and risk of suicide. JAMA Psychiatry. 2013;70(7):692-697. doi:10.1001/jamapsychiatry.2013.908
6. Frenk SM, Porter KS, Paulozzi LJ. Prescription opioid analgesic use among adults: United States, 1999-2012. National Center for Health Statistics data brief. https://www.cdc.gov/nchs/products/databriefs/db189.htm. Published February 25, 2015. Accessed July 20, 2020.
7. Bohnert ASB, Ilgen MA. Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019;380(14):71-79. doi:10.1056/NEJMc1901540
8. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152(2):85-92. doi:10.7326/0003-4819-152-2-201001190-00006
9. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686-691. doi:10.1001/archinternmed.2011.117
10. Ilgen MA, Bohnert AS, Ganoczy D, Bair MJ, McCarthy JF, Blow FC. Opioid dose and risk of suicide. Pain. 2016;157(5):1079-1084. doi:10.1097/j.pain.0000000000000484
11. Sinyor M, Howlett A, Cheung AH, Schaffer A. Substances used in completed suicide by overdose in Toronto: an observational study of coroner’s data. Can J Psychiatry. 2012;57(3):184-191. doi:10.1177/070674371205700308
12. Wilcox HC, Conner KR, Caine ED. Association of alcohol and drug use disorders and completed suicide: an empirical review of cohort studies. Drug Alcohol Depend. 2004;76(suppl):S11-S19 doi:10.1016/j.drugalcdep.2004.08.003.
13. Baser OL, Mardekian XJ, Schaaf D, Wang L, Joshi AV. Prevalence of diagnosed opioid abuse and its economic burden in the Veterans Health Administration. Pain Pract. 2014;14(5):437-445. doi:10.1111/papr.12097
14. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the united states, 1999-2015. National Center for Health Statistics data brief. https://www.cdc.gov/nchs/data/databriefs/db273.pdf. Published February 2017. Accessed July 20, 2020.
15. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. doi:10.15585/mmwr.mm655051e1
16. Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and opioid-involved overdose deaths—United States, 2013-2017. MMWR Morb Mortal Wkly Rep. 2019,67(5152):1419-1427. doi:10.15585/mmwr.mm675152e1
17. US Department of Veterans Affairs and Department of Defense. VA/DOD clinical practice guideline for opioid therapy for chronic pain version 3.0. https://www.healthquality.va.gov/guidelines/pain/cot. Updated March 1, 2018. Accessed July 20, 2020.
18. Vaughn IA, Beyth RJ, Ayers ML, et al. Multispecialty opioid risk reduction program targeting chronic pain and addiction management in veterans. Fed Pract. 2019;36(9):406-411.
19. Gellad WF, Good CB, Shulkin DJ. Addressing the opioid epidemic in the United States: lessons from the Department of Veterans Affairs. JAMA Intern Med. 2017;177(5):611-612. doi:10.1001/jamainternmed.2017.0147
20. Frank JW, Lovejoy TI, Becker WC, et al. Patient outcomes in dose reduction or discontinuation of long-term opioid therapy: a systematic review. Ann Intern Med. 2017;167(3):181-191. doi:10.7326/M17-0598
21. Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc. 2015;90(6):828-842. doi:10.1016/j.mayocp.2015.04.003
22. Veterans Health Administration, Office of Mental Health and Suicide Prevention. Opioid use and suicide risk. https://www.mentalhealth.va.gov/suicide_prevention/docs/Literature_Review_Opioid_Use_and_Suicide_Risk_508_FINAL_04-26-2019.pdf. Published April 26, 2019. Accessed July 20, 2020.
23. Demidenko MI, Dobscha SK, Morasco BJ, Meath THA, Ilgen MA, Lovejoy TI. Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. Gen Hosp Psychiatry. 2017;47:29-35. doi:10.1016/j.genhosppsych.2017.04.011
24. National Institute on Drug Abuse. Intentional versus unintentional overdose deaths. https://www.drugabuse.gov/related-topics/treatment/intentional-vs-unintentional-overdose-deaths. Updated February 13, 2017. Accessed July 20, 2020.
25. Centers for Disease Control and Prevention. Preventing suicide. https://www.cdc.gov/violenceprevention/pdf/suicide-factsheet.pdf. Published 2018. Accessed July 20, 2020.
26. Webster LR. Pain and suicide: the other side of the opioid story. Pain Med. 2014;15(3):345-346. doi:10.1111/pme.12398
Understanding De-Implementation of Low Value Castration for Men With Prostate Cancer
RESEARCH OBJECTIVE: Men with prostate cancer are often treated with androgen deprivation therapy (ADT). While ADT monotherapy is not appropriate treatment for most localized prostate cancer, it continues to be used raising questions of low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel’s Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify determinants of low value ADT use and opportunities for de-implementation strategy development.
STUDY DESIGN: We used VA national cancer registry and administrative data from 2016-2017 to select facilities with the highest and lowest rates of ADT monotherapy as localized prostate cancer treatment. We used purposive sampling to select high and low performing sites and complete and code 20 provider interviews from 14 facilities across the nation (17 high and 3 low ADT use sites). Next, we mapped TDF domains to the COM-B Model to generate a conceptual framework of provider approaches to low value ADT.
PRINCIPAL FINDINGS: Based on emerging behavioral themes, our conceptual model characterized 3 groups of providers based on low value ADT use: (1) never prescribe; (2) willing, under some circumstances, to prescribe; and (3) routinely prescribe as an acceptable treatment option. Providers in all groups demonstrated strengths in the Capability domain, such as knowledge of appropriate localized prostate cancer treatment options (knowledge), coupled with interpersonal skills to engage patients in educational discussion (skills). Motivation to prescribe low value ADT depended on goals of care, including patient preferences (goals), view of their role (beliefs in capabilities/professional role and identity), and beliefs about benefits and harms ADT would afford patients (beliefs about consequences). In the Opportunity domain, access to resources, such as guidelines and interdisciplinary colleagues (environmental resources) and advice of peers (social influences) were influential factors in providers’ decision- making about low value ADT prescribing.
CONCLUSIONS: Behavioral theory-based characterization of provider practices helps clarify determinants implicated in provider decisions to prescribe low value ADT.
IMPLICATIONS: Identifying behavioral determinants impacting provider decisions to prescribe low value ADT informs theory-based de-implementation strategy development, and serves as a model to decrease low-value care more broadly.
RESEARCH OBJECTIVE: Men with prostate cancer are often treated with androgen deprivation therapy (ADT). While ADT monotherapy is not appropriate treatment for most localized prostate cancer, it continues to be used raising questions of low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel’s Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify determinants of low value ADT use and opportunities for de-implementation strategy development.
STUDY DESIGN: We used VA national cancer registry and administrative data from 2016-2017 to select facilities with the highest and lowest rates of ADT monotherapy as localized prostate cancer treatment. We used purposive sampling to select high and low performing sites and complete and code 20 provider interviews from 14 facilities across the nation (17 high and 3 low ADT use sites). Next, we mapped TDF domains to the COM-B Model to generate a conceptual framework of provider approaches to low value ADT.
PRINCIPAL FINDINGS: Based on emerging behavioral themes, our conceptual model characterized 3 groups of providers based on low value ADT use: (1) never prescribe; (2) willing, under some circumstances, to prescribe; and (3) routinely prescribe as an acceptable treatment option. Providers in all groups demonstrated strengths in the Capability domain, such as knowledge of appropriate localized prostate cancer treatment options (knowledge), coupled with interpersonal skills to engage patients in educational discussion (skills). Motivation to prescribe low value ADT depended on goals of care, including patient preferences (goals), view of their role (beliefs in capabilities/professional role and identity), and beliefs about benefits and harms ADT would afford patients (beliefs about consequences). In the Opportunity domain, access to resources, such as guidelines and interdisciplinary colleagues (environmental resources) and advice of peers (social influences) were influential factors in providers’ decision- making about low value ADT prescribing.
CONCLUSIONS: Behavioral theory-based characterization of provider practices helps clarify determinants implicated in provider decisions to prescribe low value ADT.
IMPLICATIONS: Identifying behavioral determinants impacting provider decisions to prescribe low value ADT informs theory-based de-implementation strategy development, and serves as a model to decrease low-value care more broadly.
RESEARCH OBJECTIVE: Men with prostate cancer are often treated with androgen deprivation therapy (ADT). While ADT monotherapy is not appropriate treatment for most localized prostate cancer, it continues to be used raising questions of low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel’s Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify determinants of low value ADT use and opportunities for de-implementation strategy development.
STUDY DESIGN: We used VA national cancer registry and administrative data from 2016-2017 to select facilities with the highest and lowest rates of ADT monotherapy as localized prostate cancer treatment. We used purposive sampling to select high and low performing sites and complete and code 20 provider interviews from 14 facilities across the nation (17 high and 3 low ADT use sites). Next, we mapped TDF domains to the COM-B Model to generate a conceptual framework of provider approaches to low value ADT.
PRINCIPAL FINDINGS: Based on emerging behavioral themes, our conceptual model characterized 3 groups of providers based on low value ADT use: (1) never prescribe; (2) willing, under some circumstances, to prescribe; and (3) routinely prescribe as an acceptable treatment option. Providers in all groups demonstrated strengths in the Capability domain, such as knowledge of appropriate localized prostate cancer treatment options (knowledge), coupled with interpersonal skills to engage patients in educational discussion (skills). Motivation to prescribe low value ADT depended on goals of care, including patient preferences (goals), view of their role (beliefs in capabilities/professional role and identity), and beliefs about benefits and harms ADT would afford patients (beliefs about consequences). In the Opportunity domain, access to resources, such as guidelines and interdisciplinary colleagues (environmental resources) and advice of peers (social influences) were influential factors in providers’ decision- making about low value ADT prescribing.
CONCLUSIONS: Behavioral theory-based characterization of provider practices helps clarify determinants implicated in provider decisions to prescribe low value ADT.
IMPLICATIONS: Identifying behavioral determinants impacting provider decisions to prescribe low value ADT informs theory-based de-implementation strategy development, and serves as a model to decrease low-value care more broadly.
Trends in Colorectal Cancer Survival by Sidedness and Age in the Veterans Health Administration 2000 – 2017
BACKGROUND: Colorectal cancer (CRC) accounts for about 10% of all cancers in the VA. Three-year survival is associated with both age at diagnosis and CRC stage. Yet, the minority of cases are detected at an early stage and the overall incidence of cancer in the VA patient population is forecast to rise. CRC survival and pathogenesis differ by tumor location Increases in CRC cases in individuals younger than fifty-years-of age and at more advanced stages have been reported in large, U.S. population-based cohorts (Meester et al., 2019). Here, we present a preliminary investigation of these trends amongst CRC patients in the VA.
METHODS: Briefly, a cohort of veteran patients (n = 40,951) was identified from 2000 – 2017 using the VA Central Cancer Registry (VACCR). We required all included patients to have a histologically-confirmed case of CRC as consistent with previous studies (Zullig et al., 2016) and only one registry entry. We constructed Kaplan- Meier curves and created a Cox-Proportional Hazards model to examine survival. Additional filtering by age at the date of diagnosis was used to identify patients between ages 40 and 49 and tumor location as abstracted in the VACCR. Regression analysis was used to examine trends in stage at diagnosis and in those between aged 40 and 49.
RESULTS: Our findings indicate that proximal (rightsided) colon cancer is associated with poorer survival than distal (left-sided), consistent with previous findings. During this time period, 3% of the cohort or 1,249 cases were diagnosed amongst individuals of ages 40 – 49. Regression analysis indicated differences in trends amongst VHA patients younger than fifty years of age and in stage at diagnosis. Though, the time period of this study was shorter than those previously published.
CONCLUSION: Further work is underway to identify the sources of these differences in survivorship in VHA patients, including the analysis of therapeutic regimens. This work was performed under R&D and IRB protocols reviewed approved by the VA Boston Healthcare System.
BACKGROUND: Colorectal cancer (CRC) accounts for about 10% of all cancers in the VA. Three-year survival is associated with both age at diagnosis and CRC stage. Yet, the minority of cases are detected at an early stage and the overall incidence of cancer in the VA patient population is forecast to rise. CRC survival and pathogenesis differ by tumor location Increases in CRC cases in individuals younger than fifty-years-of age and at more advanced stages have been reported in large, U.S. population-based cohorts (Meester et al., 2019). Here, we present a preliminary investigation of these trends amongst CRC patients in the VA.
METHODS: Briefly, a cohort of veteran patients (n = 40,951) was identified from 2000 – 2017 using the VA Central Cancer Registry (VACCR). We required all included patients to have a histologically-confirmed case of CRC as consistent with previous studies (Zullig et al., 2016) and only one registry entry. We constructed Kaplan- Meier curves and created a Cox-Proportional Hazards model to examine survival. Additional filtering by age at the date of diagnosis was used to identify patients between ages 40 and 49 and tumor location as abstracted in the VACCR. Regression analysis was used to examine trends in stage at diagnosis and in those between aged 40 and 49.
RESULTS: Our findings indicate that proximal (rightsided) colon cancer is associated with poorer survival than distal (left-sided), consistent with previous findings. During this time period, 3% of the cohort or 1,249 cases were diagnosed amongst individuals of ages 40 – 49. Regression analysis indicated differences in trends amongst VHA patients younger than fifty years of age and in stage at diagnosis. Though, the time period of this study was shorter than those previously published.
CONCLUSION: Further work is underway to identify the sources of these differences in survivorship in VHA patients, including the analysis of therapeutic regimens. This work was performed under R&D and IRB protocols reviewed approved by the VA Boston Healthcare System.
BACKGROUND: Colorectal cancer (CRC) accounts for about 10% of all cancers in the VA. Three-year survival is associated with both age at diagnosis and CRC stage. Yet, the minority of cases are detected at an early stage and the overall incidence of cancer in the VA patient population is forecast to rise. CRC survival and pathogenesis differ by tumor location Increases in CRC cases in individuals younger than fifty-years-of age and at more advanced stages have been reported in large, U.S. population-based cohorts (Meester et al., 2019). Here, we present a preliminary investigation of these trends amongst CRC patients in the VA.
METHODS: Briefly, a cohort of veteran patients (n = 40,951) was identified from 2000 – 2017 using the VA Central Cancer Registry (VACCR). We required all included patients to have a histologically-confirmed case of CRC as consistent with previous studies (Zullig et al., 2016) and only one registry entry. We constructed Kaplan- Meier curves and created a Cox-Proportional Hazards model to examine survival. Additional filtering by age at the date of diagnosis was used to identify patients between ages 40 and 49 and tumor location as abstracted in the VACCR. Regression analysis was used to examine trends in stage at diagnosis and in those between aged 40 and 49.
RESULTS: Our findings indicate that proximal (rightsided) colon cancer is associated with poorer survival than distal (left-sided), consistent with previous findings. During this time period, 3% of the cohort or 1,249 cases were diagnosed amongst individuals of ages 40 – 49. Regression analysis indicated differences in trends amongst VHA patients younger than fifty years of age and in stage at diagnosis. Though, the time period of this study was shorter than those previously published.
CONCLUSION: Further work is underway to identify the sources of these differences in survivorship in VHA patients, including the analysis of therapeutic regimens. This work was performed under R&D and IRB protocols reviewed approved by the VA Boston Healthcare System.
Thromboembolic Events in Lung Cancer Patients Treated With Conventional Chemotherapy Alone Compared With Immunotherapy
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
The Importance of Adjuvant Treatment and Primary Anatomical Site in Head and Neck Basaloid Squamous Cell Carcinoma Survival: An Analysis of the National Cancer Database
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that account for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within basaloid squamous cell carcinoma subtype and its impact on survival.
METHODS: A cohort of 1,999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy.
RESULTS: In this cohort, 82% were male with a median age of 59 years. The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The majority of the cohort had stage IV disease, while 3.9% had metastases. The presence of metastasis increased probability of mortality (HR=2.14; 95% CI: 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR=2.45; 95% CI: 1.83-3.29), hypopharynx (HR=2.58; 95% CI: 1.64-4.05), and larynx (HR=2.89; 95% CI: 2.25-3.73). Adjuvant chemoradiation (HR=0.36; 95% CI: 0.23-0.58) and adjuvant radiation (HR=0.38; 95% CI: 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy alone. Patients with microscopic tumor margins had better survival outcomes when compared to no surgery (HR=0.38, 98% Cl: 0.23-0.64) while there was no better survival outcomes of patients with macroscopic margins compared to no surgery.
CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, microscopic margins or residual tumor were associated with greater survival. This study demonstrates the importance of these factors as independent prognostic factors when considering survival of patients diagnosed with BSCC of the head and neck.
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that account for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within basaloid squamous cell carcinoma subtype and its impact on survival.
METHODS: A cohort of 1,999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy.
RESULTS: In this cohort, 82% were male with a median age of 59 years. The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The majority of the cohort had stage IV disease, while 3.9% had metastases. The presence of metastasis increased probability of mortality (HR=2.14; 95% CI: 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR=2.45; 95% CI: 1.83-3.29), hypopharynx (HR=2.58; 95% CI: 1.64-4.05), and larynx (HR=2.89; 95% CI: 2.25-3.73). Adjuvant chemoradiation (HR=0.36; 95% CI: 0.23-0.58) and adjuvant radiation (HR=0.38; 95% CI: 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy alone. Patients with microscopic tumor margins had better survival outcomes when compared to no surgery (HR=0.38, 98% Cl: 0.23-0.64) while there was no better survival outcomes of patients with macroscopic margins compared to no surgery.
CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, microscopic margins or residual tumor were associated with greater survival. This study demonstrates the importance of these factors as independent prognostic factors when considering survival of patients diagnosed with BSCC of the head and neck.
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that account for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within basaloid squamous cell carcinoma subtype and its impact on survival.
METHODS: A cohort of 1,999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy.
RESULTS: In this cohort, 82% were male with a median age of 59 years. The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The majority of the cohort had stage IV disease, while 3.9% had metastases. The presence of metastasis increased probability of mortality (HR=2.14; 95% CI: 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR=2.45; 95% CI: 1.83-3.29), hypopharynx (HR=2.58; 95% CI: 1.64-4.05), and larynx (HR=2.89; 95% CI: 2.25-3.73). Adjuvant chemoradiation (HR=0.36; 95% CI: 0.23-0.58) and adjuvant radiation (HR=0.38; 95% CI: 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy alone. Patients with microscopic tumor margins had better survival outcomes when compared to no surgery (HR=0.38, 98% Cl: 0.23-0.64) while there was no better survival outcomes of patients with macroscopic margins compared to no surgery.
CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, microscopic margins or residual tumor were associated with greater survival. This study demonstrates the importance of these factors as independent prognostic factors when considering survival of patients diagnosed with BSCC of the head and neck.
The Impact of Sequencing of Abiraterone and Enzalutamide in Veterans With Metastatic Castration- Resistant Prostate Cancer
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC). BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC). BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC). BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
The Impact of Sequencing of Abiraterone and Enzalutamide in Veterans With Metastatic Castration- Resistant Prostate Cancer
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC).
BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC).
BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC).
BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
The Effect of Treatment Facility and Race on Survival for Signet Ring Cell Carcinoma of the Esophagus: An Analysis of the National Cancer Database
BACKGROUND: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility.
METHODS: There were 1,442 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance and impact of treatment facility type, race, age, sex, tumor stage, use of adjuvant or neoadjuvant radiation, and surgical margins on survival.
RESULTS: The cohort was mostly male (86.6%) and Non-Hispanic Caucasian (96.3%) with 52.7% receiving treatment at academic centers followed by 35.9% at community programs and 11.4% at integrated cancer programs. As age increased, mortality also increased (HR = 1.02; 95% CI: 1.01-1.02, p < 0.001). Both Hispanic Caucasians (HR = 2.09; 95% CI: 1.21-3.62, = 0.009) and Africans Americans (HR = 1.69; 95% CI: 1.04-2.75, = 0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programs (HR = 0.73; 95% CI: 0.63-0.86, p < 0.001) and integrated cancer programs (HR = 0.74; 95% CI: 0.60- 0.93, = 0.008).
CONCLUSION: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans and Hispanic Caucasians, increasing tumor stage, positive surgical margins, and comorbidities with Charlson- Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
BACKGROUND: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility.
METHODS: There were 1,442 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance and impact of treatment facility type, race, age, sex, tumor stage, use of adjuvant or neoadjuvant radiation, and surgical margins on survival.
RESULTS: The cohort was mostly male (86.6%) and Non-Hispanic Caucasian (96.3%) with 52.7% receiving treatment at academic centers followed by 35.9% at community programs and 11.4% at integrated cancer programs. As age increased, mortality also increased (HR = 1.02; 95% CI: 1.01-1.02, p < 0.001). Both Hispanic Caucasians (HR = 2.09; 95% CI: 1.21-3.62, = 0.009) and Africans Americans (HR = 1.69; 95% CI: 1.04-2.75, = 0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programs (HR = 0.73; 95% CI: 0.63-0.86, p < 0.001) and integrated cancer programs (HR = 0.74; 95% CI: 0.60- 0.93, = 0.008).
CONCLUSION: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans and Hispanic Caucasians, increasing tumor stage, positive surgical margins, and comorbidities with Charlson- Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
BACKGROUND: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility.
METHODS: There were 1,442 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance and impact of treatment facility type, race, age, sex, tumor stage, use of adjuvant or neoadjuvant radiation, and surgical margins on survival.
RESULTS: The cohort was mostly male (86.6%) and Non-Hispanic Caucasian (96.3%) with 52.7% receiving treatment at academic centers followed by 35.9% at community programs and 11.4% at integrated cancer programs. As age increased, mortality also increased (HR = 1.02; 95% CI: 1.01-1.02, p < 0.001). Both Hispanic Caucasians (HR = 2.09; 95% CI: 1.21-3.62, = 0.009) and Africans Americans (HR = 1.69; 95% CI: 1.04-2.75, = 0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programs (HR = 0.73; 95% CI: 0.63-0.86, p < 0.001) and integrated cancer programs (HR = 0.74; 95% CI: 0.60- 0.93, = 0.008).
CONCLUSION: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans and Hispanic Caucasians, increasing tumor stage, positive surgical margins, and comorbidities with Charlson- Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
Sequential Targeted Treatment of an Elderly Patient With Acute Myeloid Leukemia Harboring Concurrent FLT3-TKD and IDH1 Mutations: A Case Report
INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.
CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.
CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.
INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.
CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.
CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.
INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.
CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.
CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.
In-Depth Look at a Community- Based Population of Multiple Myeloma (MM) Patients Undergoing an in-Class Transition (iCT) from Parenteral Bortezomib to Oral Ixazomib in the United States (US) MM-6 Study
BACKGROUND: Randomized clinical trials (RCTs) typically enroll highly selected populations. Oncology RCTs have an average of 16 eligibility criteria (Unger JNCI 2014). Registry analyses indicate that up to ~40% of ‘real-world’ MM patients are ineligible for RCTs based on common criteria (Shah CLML 2017).
PURPOSE: US MM-6 (NCT03173092) is evaluating iCT from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in MM patients treated at US community oncology centers. Eligibility criteria are less stringent than RCTs, to enroll patients more representative of the real-world MM population.
METHODS: Non-transplant-eligible newly-diagnosed MM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at 22 US community sites (including three Veterans Affairs hospitals) to receive ixazomib-Rd for up to 39 28- day cycles or until progression/toxicity.
DATA ANALYSIS: We reviewed 84 consecutively enrolled patients using standard RCT eligibility criteria. Initially, six criteria were explored to determine the proportion of patients who might have been RCT-ineligible: renal dysfunction, congestive heart failure (CHF), stroke, prior malignancies, chronic obstructive pulmonary disease (COPD), and memory loss. Dosing information was evaluated to determine any correlation between dose modifications and eligibility status.
RESULTS: Based on six criteria, 24/84 patients (29%) may have been RCT-ineligible: 12% (n=10) had renal dysfunction, 7% (n=6) CHF, 6% (n=5) stroke, 5% (n=4) each other prior malignancies and COPD, and 2% (n=2) memory loss; 6% (n=5) had >1 criterion. Among the 24 RCT-ineligible patients, 75% (n=18), 42% (n=10), and 54% (n=13) received the highest starting doses of ixazomib (4mg), lenalidomide (25mg), and dexamethasone (40mg), respectively. Ixazomib, lenalidomide, and dexamethasone dose reductions were required in 29% (n=7), 25% (n=6), and 21% (n=5), respectively (due to adverse events [AEs]: 21% [n=5], 21% [n=5], 4% [n=1]). 50% (n=12) discontinued treatment (consent withdrawal/patient decision, n=7; disease progression, n=2; sufficient response, AE, death, each n=1); n=3/2/2 discontinued ixazomib/lenalidomide/ dexamethasone due to AEs.
IMPLICATIONS: US MM-6 is enrolling real-world, community- based MM patients, including those who may be ineligible for RCTs based on standard inclusion criteria. Our analysis indicates that iCT to ixazomib- Rd appears to be feasible in these RCT-ineligible US MM-6 patients. Further criteria will be analyzed and presented.
BACKGROUND: Randomized clinical trials (RCTs) typically enroll highly selected populations. Oncology RCTs have an average of 16 eligibility criteria (Unger JNCI 2014). Registry analyses indicate that up to ~40% of ‘real-world’ MM patients are ineligible for RCTs based on common criteria (Shah CLML 2017).
PURPOSE: US MM-6 (NCT03173092) is evaluating iCT from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in MM patients treated at US community oncology centers. Eligibility criteria are less stringent than RCTs, to enroll patients more representative of the real-world MM population.
METHODS: Non-transplant-eligible newly-diagnosed MM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at 22 US community sites (including three Veterans Affairs hospitals) to receive ixazomib-Rd for up to 39 28- day cycles or until progression/toxicity.
DATA ANALYSIS: We reviewed 84 consecutively enrolled patients using standard RCT eligibility criteria. Initially, six criteria were explored to determine the proportion of patients who might have been RCT-ineligible: renal dysfunction, congestive heart failure (CHF), stroke, prior malignancies, chronic obstructive pulmonary disease (COPD), and memory loss. Dosing information was evaluated to determine any correlation between dose modifications and eligibility status.
RESULTS: Based on six criteria, 24/84 patients (29%) may have been RCT-ineligible: 12% (n=10) had renal dysfunction, 7% (n=6) CHF, 6% (n=5) stroke, 5% (n=4) each other prior malignancies and COPD, and 2% (n=2) memory loss; 6% (n=5) had >1 criterion. Among the 24 RCT-ineligible patients, 75% (n=18), 42% (n=10), and 54% (n=13) received the highest starting doses of ixazomib (4mg), lenalidomide (25mg), and dexamethasone (40mg), respectively. Ixazomib, lenalidomide, and dexamethasone dose reductions were required in 29% (n=7), 25% (n=6), and 21% (n=5), respectively (due to adverse events [AEs]: 21% [n=5], 21% [n=5], 4% [n=1]). 50% (n=12) discontinued treatment (consent withdrawal/patient decision, n=7; disease progression, n=2; sufficient response, AE, death, each n=1); n=3/2/2 discontinued ixazomib/lenalidomide/ dexamethasone due to AEs.
IMPLICATIONS: US MM-6 is enrolling real-world, community- based MM patients, including those who may be ineligible for RCTs based on standard inclusion criteria. Our analysis indicates that iCT to ixazomib- Rd appears to be feasible in these RCT-ineligible US MM-6 patients. Further criteria will be analyzed and presented.
BACKGROUND: Randomized clinical trials (RCTs) typically enroll highly selected populations. Oncology RCTs have an average of 16 eligibility criteria (Unger JNCI 2014). Registry analyses indicate that up to ~40% of ‘real-world’ MM patients are ineligible for RCTs based on common criteria (Shah CLML 2017).
PURPOSE: US MM-6 (NCT03173092) is evaluating iCT from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in MM patients treated at US community oncology centers. Eligibility criteria are less stringent than RCTs, to enroll patients more representative of the real-world MM population.
METHODS: Non-transplant-eligible newly-diagnosed MM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at 22 US community sites (including three Veterans Affairs hospitals) to receive ixazomib-Rd for up to 39 28- day cycles or until progression/toxicity.
DATA ANALYSIS: We reviewed 84 consecutively enrolled patients using standard RCT eligibility criteria. Initially, six criteria were explored to determine the proportion of patients who might have been RCT-ineligible: renal dysfunction, congestive heart failure (CHF), stroke, prior malignancies, chronic obstructive pulmonary disease (COPD), and memory loss. Dosing information was evaluated to determine any correlation between dose modifications and eligibility status.
RESULTS: Based on six criteria, 24/84 patients (29%) may have been RCT-ineligible: 12% (n=10) had renal dysfunction, 7% (n=6) CHF, 6% (n=5) stroke, 5% (n=4) each other prior malignancies and COPD, and 2% (n=2) memory loss; 6% (n=5) had >1 criterion. Among the 24 RCT-ineligible patients, 75% (n=18), 42% (n=10), and 54% (n=13) received the highest starting doses of ixazomib (4mg), lenalidomide (25mg), and dexamethasone (40mg), respectively. Ixazomib, lenalidomide, and dexamethasone dose reductions were required in 29% (n=7), 25% (n=6), and 21% (n=5), respectively (due to adverse events [AEs]: 21% [n=5], 21% [n=5], 4% [n=1]). 50% (n=12) discontinued treatment (consent withdrawal/patient decision, n=7; disease progression, n=2; sufficient response, AE, death, each n=1); n=3/2/2 discontinued ixazomib/lenalidomide/ dexamethasone due to AEs.
IMPLICATIONS: US MM-6 is enrolling real-world, community- based MM patients, including those who may be ineligible for RCTs based on standard inclusion criteria. Our analysis indicates that iCT to ixazomib- Rd appears to be feasible in these RCT-ineligible US MM-6 patients. Further criteria will be analyzed and presented.